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Are Cholesterol Tests Always Accurate?

Title: Are Cholesterol Tests Always Accurate?
Category: Diseases and Conditions
Created: 3/9/2022 12:00:00 AM
Last Editorial Review: 3/9/2022 12:00:00 AM




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Which Nuts Are Best to Lower Cholesterol?

Title: Which Nuts Are Best to Lower Cholesterol?
Category: Diseases and Conditions
Created: 5/10/2022 12:00:00 AM
Last Editorial Review: 5/10/2022 12:00:00 AM




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Are Plant Sterols Good for Lowering Cholesterol?

Title: Are Plant Sterols Good for Lowering Cholesterol?
Category: Diseases and Conditions
Created: 5/12/2022 12:00:00 AM
Last Editorial Review: 5/12/2022 12:00:00 AM




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Does Coffee Raise Cholesterol?

Title: Does Coffee Raise Cholesterol?
Category: Health News
Created: 5/11/2022 12:00:00 AM
Last Editorial Review: 5/12/2022 12:00:00 AM




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Gene Tests Could Spot 1 Million Americans at Risk of High Cholesterol

Title: Gene Tests Could Spot 1 Million Americans at Risk of High Cholesterol
Category: Health News
Created: 5/18/2022 12:00:00 AM
Last Editorial Review: 5/18/2022 12:00:00 AM




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What Fish Is Best for Lowering Cholesterol?

Title: What Fish Is Best for Lowering Cholesterol?
Category: Health and Living
Created: 5/19/2022 12:00:00 AM
Last Editorial Review: 5/19/2022 12:00:00 AM




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26 Natural Ways to Lower Your Cholesterol Levels

Title: 26 Natural Ways to Lower Your Cholesterol Levels
Category: Health and Living
Created: 7/6/2022 12:00:00 AM
Last Editorial Review: 7/6/2022 12:00:00 AM




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What Can You Eat on a Low Cholesterol Diet?

Title: What Can You Eat on a Low Cholesterol Diet?
Category: Health and Living
Created: 8/27/2021 12:00:00 AM
Last Editorial Review: 7/6/2022 12:00:00 AM




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Cholesterol Management

Title: Cholesterol Management
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 7/6/2022 12:00:00 AM




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Lifestyle May Be Key to Helping You Avoid Dementia

Title: Lifestyle May Be Key to Helping You Avoid Dementia
Category: Health News
Created: 8/4/2022 12:00:00 AM
Last Editorial Review: 8/5/2022 12:00:00 AM




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People Underestimate Impact of Random Acts of Kindness

Title: People Underestimate Impact of Random Acts of Kindness
Category: Health News
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/25/2022 12:00:00 AM




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CDC Investigating E. coli Outbreak in Ohio, Michigan

Title: CDC Investigating E. coli Outbreak in Ohio, Michigan
Category: Health News
Created: 8/18/2022 12:00:00 AM
Last Editorial Review: 8/19/2022 12:00:00 AM




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84 People Now Sickened in E. Coli Outbreak Tied to Wendy's Restaurant Lettuce

Title: 84 People Now Sickened in E. Coli Outbreak Tied to Wendy's Restaurant Lettuce
Category: Health News
Created: 8/26/2022 12:00:00 AM
Last Editorial Review: 8/26/2022 12:00:00 AM




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12 Best Compression Leggings in 2022

Title: 12 Best Compression Leggings in 2022
Category: Health and Living
Created: 8/16/2022 12:00:00 AM
Last Editorial Review: 8/16/2022 12:00:00 AM




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HIV Testing Plummeted During Pandemic

Title: HIV Testing Plummeted During Pandemic
Category: Health News
Created: 6/27/2022 12:00:00 AM
Last Editorial Review: 6/27/2022 12:00:00 AM




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What Time of Day Is Blood Pressure Highest?

Title: What Time of Day Is Blood Pressure Highest?
Category: Diseases and Conditions
Created: 7/14/2022 12:00:00 AM
Last Editorial Review: 7/14/2022 12:00:00 AM




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When Is Blood Pressure Lowest and Highest During the Day?

Title: When Is Blood Pressure Lowest and Highest During the Day?
Category: Diseases and Conditions
Created: 7/26/2022 12:00:00 AM
Last Editorial Review: 7/26/2022 12:00:00 AM




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SIBO (Small Intestinal Bacterial Overgrowth)

Title: SIBO (Small Intestinal Bacterial Overgrowth)
Category: Diseases and Conditions
Created: 10/28/2005 12:00:00 AM
Last Editorial Review: 8/8/2022 12:00:00 AM




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Organ From Live Donor Best When Child Needs New Kidney

Title: Organ From Live Donor Best When Child Needs New Kidney
Category: Health News
Created: 8/17/2022 12:00:00 AM
Last Editorial Review: 8/18/2022 12:00:00 AM




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Digestive Enzymes Oral

Title: Digestive Enzymes Oral
Category: Medications
Created: 3/2/2005 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM




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How to Get Rid of Mucus in My Chest Fast

Title: How to Get Rid of Mucus in My Chest Fast
Category: Diseases and Conditions
Created: 6/22/2022 12:00:00 AM
Last Editorial Review: 6/22/2022 12:00:00 AM




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The chromatin tapestry as a framework for neurodevelopment [MINI-REVIEW]

The neuronal nucleus houses a meticulously organized genome. Within this structure, genetic material is not simply compacted but arranged into a precise and functional 3D chromatin landscape essential for cellular regulation. This mini-review highlights the importance of this chromatin landscape in healthy neurodevelopment, as well as the diseases that occur with aberrant chromatin architecture. We discuss insights into the fundamental mechanistic relationship between histone modifications, DNA methylation, and genome organization. We then discuss findings that reveal how these epigenetic features change throughout normal neurodevelopment. Finally, we highlight single-gene neurodevelopmental disorders that illustrate the interdependence of epigenetic features, showing how disruptions in DNA methylation or genome architecture can ripple across the entire epigenome. As such, we emphasize the importance of measuring multiple chromatin architectural aspects, as the disruption of one mechanism can likely impact others in the intricate epigenetic network. This mini-review underscores the vast gaps in our understanding of chromatin structure in neurodevelopmental diseases and the substantial research needed to understand the interplay between chromatin features and neurodevelopment.




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Impact of Point of Care Hemoglobin A1c Testing on Time to Therapeutic Intervention

Without compromising accuracy, point of care testing (POCT) provides immediate results at the time of in person patient consultation. The purpose of this study was to evaluate time until therapeutic intervention with POCT HbA1c versus venipuncture, where venipuncture was considered standard of care.

The primary outcome was time (hours) to implementation of a therapeutic intervention based on POCT HbA1c result, as compared with most recent venipuncture HbA1c before the study and its associated therapeutic intervention. A total of 94 POCT HbA1c tests were included in the primary analysis.

For the POCT HbA1c, the mean time to therapeutic intervention was 1.6 ± 3.14 hours. For the previous venipuncture HbA1c, the mean time to therapeutic intervention was 1376.66 ± 3356.6 hours (P < .001). Overall, this trial showed that POCT HbA1c results in a significantly faster time to therapeutic intervention than venipuncture in a primary care clinic that serves a rural population.




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Primary Care Clinicians' Interest In, and Barriers To, Medication Abortion

Purpose:

Providing medication abortion in the primary care setting is a promising way to increase access to abortion, a threatened service in many States. This study aimed to characterize primary care clinicians’ interest in prescribing medication abortion, what barriers they face in adding this service, and what support they need.

Methods:

Data were collected from 162 practicing primary care clinicians in Minnesota using an online survey with closed- and open-ended response options. Data were analyzed using descriptive statistics, group comparison analyses, and content analysis for the open-ended questions.

Results:

Participants represented a diverse range of ages, years in practice, credentials, genders, and urban/rural practice settings, and held mixed knowledge and attitudes around medication abortion. All demographic groups surveyed expressed interest in prescribing medication abortion, with the strongest interest represented among younger respondents, women, and those practicing in urban settings. Clinicians who provide prenatal care or who already work with these medications in other contexts were more likely to want to add medication abortion to their practices. The most common barrier to providing medication abortion was a lack of knowledge about organizational policies and about the medications themselves. To empower clinicians to provide medication abortion, respondents voiced needing their health systems to build clear processes and wanting supportive networks of other clinicians for collaboration.

Conclusions:

Given the interest of primary care clinicians in providing medication abortion, health systems have a valuable opportunity to increase access.




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Simulation in Mechanical Ventilation Training: Integrating Best Practices for Effective Education




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Perspectives on Using Race in Pulmonary Function Testing: A National Survey of Fellows and Program Directors

BACKGROUND:Pulmonary function tests (PFTs) have historically used race-specific prediction equations. The recent American Thoracic Society guidelines recommend the use of a race-neutral approach in prediction equations. There are limited studies centering the opinions of practicing pulmonologists on the use of race in spirometry. Provider opinion will impact adoption of the new guideline. The aim of this study was to ascertain the beliefs of academic pulmonary and critical care providers regarding the use of race as a variable in spirometry prediction equations.METHODS:We report data from 151 open-ended responses from a voluntary, nationwide survey (distributed by the Association of Pulmonary Critical Care Medicine Program Directors) of academic pulmonary and critical care providers regarding the use of race in PFT prediction equations. Responses were coded using inductive and deductive methods, and a thematic content analysis was conducted.RESULTS:There was a balanced distribution of opinions among respondents supporting, opposing, or being unsure about the incorporation of race in spirometry prediction equations. Responses demonstrated a wide array of understanding related to the concept and definition of race and its relationship to physiology.CONCLUSIONS:There was no consensus among providers regarding the use of race in spirometry prediction equations. Concepts of race having biologic implications persist among pulmonary providers and will likely affect the uptake of the Global Lung Function Initiative per the American Thoracic Society guidelines.




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Deciphering visceral instincts: a scientific quest to unravel food choices from molecules to mind [Special Section: Symposium Outlook]

The study of biological mechanisms, while crucial, cannot fully explain complex phenomena like the instinct to eat. The mind–body connection, as exemplified by the concept of "voodoo death," highlights the profound influence of belief and cultural context on physiology. Indigenous knowledge systems further emphasize the interconnectedness of humans with their environment. Recent discoveries in gut–brain communication reveal the intricate neural circuits that drive our visceral desires, but a holistic approach that integrates both physiological mechanisms and the subjective experience of life, informed by diverse cultural perspectives, will be essential to truly understand what it means to be alive.




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Longitudinal validation of King's Sarcoidosis Questionnaire in a prospective cohort with mild sarcoidosis

Background

Quality of life is impaired in patients with sarcoidosis. The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health-related quality of life in patients with sarcoidosis, comprising subdomains of General Health Status (GHS), Lung, Medication, Skin and Eyes. The aim of this study was to enhance the validation of the KSQ, incorporating longitudinal validation and known-groups validity in a cohort with mild sarcoidosis.

Methods

The KSQ was linguistically validated according to guidelines. Patients with sarcoidosis completed KSQ and other questionnaires at baseline, after 2 weeks and at 12 months. Forced vital capacity (FVC) was measured. Concurrent validity, reliability and responsiveness were assessed.

Results

In patients (n=150), the KSQ had moderate to strong correlations with the Short Form-12 (Mental Component Summary), the King's Brief Interstitial Lung Disease questionnaire and the Fatigue Assessment Scale (r=0.30–0.70) and weak correlations with the Short Form-12 (Physical Component Summary) and FVC (r=0.01–0.29). The KSQ GHS and Lung domains were able to discriminate between groups of patients stratified according to fatigue, treatment and FVC. The KSQ had high internal consistency (Cronbach's α=0.73–0.90) and repeatability (interclass correlation coefficients 0.72–0.81). Correlations to comparable questionnaires at baseline were moderate or strong for the GHS, Lung and GHS–Lung subdomains and weak or moderate for FVC. The KSQ was responsive to changes over time.

Conclusion

This study strengthened the validation of the KSQ by introducing known-groups validity and assessments of responsiveness over 12 months in patients with mild sarcoidosis.




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Accuracy of CAD4TB (Computer-Aided Detection for Tuberculosis) on paediatric chest radiographs

Background

Computer-aided detection (CAD) systems hold promise for improving tuberculosis (TB) detection on digital chest radiographs. However, data on their performance in exclusively paediatric populations are scarce.

Methods

We conducted a retrospective diagnostic accuracy study evaluating the performance of CAD4TBv7 (Computer-Aided Detection for Tuberculosis version 7) using digital chest radiographs from well-characterised cohorts of Gambian children aged <15 years with presumed pulmonary TB. The children were consecutively recruited between 2012 and 2022. We measured CAD4TBv7 performance against a microbiological reference standard (MRS) of confirmed TB, and also performed Bayesian latent class analysis (LCA) to address the inherent limitations of the MRS in children. Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUROC) and point estimates of sensitivity and specificity.

Results

A total of 724 children were included in the analysis, with confirmed TB in 58 (8%), unconfirmed TB in 145 (20%) and unlikely TB in 521 (72%). Using the MRS, CAD4TBv7 showed an AUROC of 0.70 (95% CI 0.60–0.79), and demonstrated sensitivity and specificity of 19.0% (95% CI 11–31%) and 99.0% (95% CI 98.0–100.0%), respectively. Applying Bayesian LCA with the assumption of conditional independence between tests, sensitivity and specificity estimates for CAD4TBv7 were 42.7% (95% CrI 29.2–57.5%) and 97.9% (95% CrI 96.6–98.8%), respectively. When allowing for conditional dependence between culture and Xpert assay, CAD4TBv7 demonstrated a sensitivity of 50.3% (95% CrI 32.9–70.0%) and specificity of 98.0% (95% CrI 96.7–98.9%).

Conclusion

Although CAD4TBv7 demonstrated high specificity, its suboptimal sensitivity underscores the crucial need for optimisation of CAD4TBv7 for detecting TB in children.




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Investigations into the Concentrations and Metabolite Profiles of Doping Agents and Antidepressants in Human Seminal Fluid Using Liquid Chromatography-Mass Spectrometry [Articles]

Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid and influence male fertility and reproduction. In addition, substances relevant in the context of sports drug testing programs, can be transferred into the urine of a female athlete (after unprotected sexual intercourse) and trigger a so-called adverse analytical finding. Here, the question arises as to whether it is possible to distinguish analytically between intentional doping offenses and unintentional contamination of urine by seminal fluid. To this end, 480 seminal fluids from nonathletes were analyzed to identify concentration ranges and metabolite profiles of therapeutic drugs that are also classified as doping agents. Therefore, a screening procedure was developed using liquid chromatography connected to a triple quadrupole mass spectrometer, and suspect samples (i.e., samples indicating the presence of relevant compounds) were further subjected to liquid chromatography-high-resolution accurate mass (tandem) mass spectrometry. The screening method yielded 90 findings (including aromatase inhibitors, selective estrogen receptor modulators, diuretics, stimulants, glucocorticoids, beta-blockers, antidepressants, and the nonapproved proliferator-activated receptor delta agonist GW1516) in a total of 81 samples, with 91% of these suspected cases being verified by the confirmation method. In addition to the intact drug, phase-I and -II metabolites were also occasionally observed in the seminal fluid. This study demonstrated that various drugs including those categorized as doping agents partition into seminal fluid. Monitoring substances and metabolites may contribute to a better understanding of the distribution and metabolism of exogenous substances in seminal fluid that may be responsible for the impairment of male fertility.

SIGNIFICANCE STATEMENT

This study demonstrates that doping agents as well as clinically relevant substances are transferred/eliminated into seminal fluid to a substantial extent and that knowledge about drug levels (and potential consequences for the male fertility and female exposure) is limited. The herein generated new dataset provides new insights into an important and yet little explored area of drug deposition and elimination, and hereby a basis for the assessment of contamination cases by seminal fluid in sports drug testing.




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Establishment of the First Institution-Based Poison Information Center in Nepal Through a Multilateral International Partnership

ABSTRACTToxicological emergencies present a significant health challenge in Nepal. Despite the high burden, the country has inadequate formal toxicology training, medical toxicology expertise, and adequate poison control infrastructure. In recognition of this need, the Nepal Poison Information Center (PIC) was established as a collaborative effort involving local and international partners. Through a comprehensive partnership framework, the Nepal PIC provides 24 hours a day, 7 days a week expert guidance to health care workers, conducts educational webinars, and engages in research. Initial data from the pilot phase indicate successful consultation delivery. Challenges include bureaucratic hurdles and the need for sustainable funding. Despite these challenges, the Nepal PIC demonstrates early feasibility and potential for expansion into a comprehensive toxicology center, contributing to the advancement of clinical toxicology in Nepal. Long-term sustainability relies on governmental support and continued advocacy efforts.




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Improving Maternity Care Where Home Births Are Still the Norm: Establishing Local Birthing Centers in Guatemala That Incorporate Traditional Midwives

ABSTRACTMore than half of births among Indigenous women in Guatemala are still being attended at home by providers with no formal training. We describe the incorporation of comadronas (traditional midwives) into casas maternas (birthing centers) in the rural highlands of western Guatemala. Although there was initial resistance to the casa, comadronas and clients have become increasingly enthusiastic about them. The casas provide the opportunity for comadronas to continue the cultural traditions of prayers, massages, and other practices that honor the vital spiritual dimension of childbirth close to home in a home-like environment with extended family support while at the same time providing a safer childbirth experience in which complications can be detected by trained personnel at the casa, managed locally, or promptly referred to a higher-level facility. Given the growing acceptance of this innovation in an environment in which geographical, financial, and cultural barriers to deliveries at higher-level facilities lead most women to deliver at home, casas maternas represent a feasible option for reducing the high level of maternal mortality in Guatemala.This article provides an update on the growing utilization of casas and provides new insights into the role of comadronas as birthing team members and enthusiastic promotors of casas maternas as a preferable alternative to home births. Through the end of 2023, these casas maternas had cared for 4,322 women giving birth. No maternal deaths occurred at a casa, but 4 died after referral.The Ministry of Health of Guatemala has recently adopted this approach and has begun to implement it in other rural areas where home births still predominate. This approach deserves consideration as a viable and feasible option for reducing maternal mortality throughout the world where home births are still common, while at the same time providing women with respectful and culturally appropriate care.




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Innovations in Providing HIV Index Testing Services: A Retrospective Evaluation of Partner Elicitation Models in Southern Nigeria

ABSTRACTBackground: This analysis aimed to evaluate the effectiveness of eliciting sexual partners from HIV-positive clients using the elicitation box model (where an HIV-positive index can report sexual contacts on paper and insert in a box for a health care provider to contact at a later time) compared to the conventional model (in which a health care provider elicits sexual contacts directly from clients) in Akwa Ibom, Southern Nigeria.Methods: Between March 2021 and April 2022, data were collected from index testing registers at 4 health facilities with a high volume of HIV clients currently on treatment in 4 local government areas in Akwa Ibom State. Primary outcome analyzed was the elicitation ratio (number of partners elicited per HIV-index offered index testing services). Secondary outcomes were the index testing acceptance (index HIV-positive clients accepted index testing service), testing coverage (partners tested for HIV from a list of partners elicited from HIV-index accepted index testing services), testing yield (index partners identified HIV positive from index partners HIV-tested), and linkage rate (index partners identified HIV positive and linked to antiretroviral therapy).Results: Of the total 2,705 index clients offered index testing services, 91.9% accepted, with 2,043 and 439 indexes opting for conventional elicitation and elicitation box models, respectively. A total of 3,796 sexual contacts were elicited: 2,546 using the conventional model (elicitation ratio=1:1) and 1,250 using the elicitation box model (elicitation ratio=1:3). Testing coverage was significantly higher in the conventional compared to the elicitation box model (P<.001). However, there was no significant difference in the testing yield (P=.81) and linkage rate using the conventional compared to elicitation box models (P=.13).Conclusion: The implementation of the elicitation box model resulted in an increase in partner elicitation compared to the conventional model. Increasing the testing coverage by implementing the elicitation box model should be considered.




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No In Vivo Evidence for Estrogen Receptor Density Changes in Human Neuroendocrine Aging or Their Relationship to Cognition and Menopausal Symptoms




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Preclinical Investigation of [212Pb]Pb-DOTAM-GRPR1 for Peptide Receptor Radionuclide Therapy in a Prostate Tumor Model

The role of gastrin-releasing peptide receptor (GRPR) in various diseases, including cancer, has been extensively studied and has emerged as a promising therapeutic target. In this study, we successfully achieved the use of [212Pb]Pb-DOTAM-GRPR1, comprising the α-particle generator, 212Pb, combined with a GRPR-targeting peptide, GRPR1, in a prostate cancer model. Methods: Pharmacokinetics, toxicity, radiation dosimetry, and efficacy were assessed in GRPR-positive prostate tumor–bearing mice after intravenous administration of [212Pb]Pb-DOTAM-GRPR1 (where DOTAM is 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). Results: Preclinical studies have shown tumor targeting of up to 5 percent injected dose per gram over 24 h, and optimization of the drug formulation and quantity has led to minimized oxidation and off-target binding, respectively. Particularly, an increase in peptide amount from 28 to 280 ng was shown to reduce off-target uptake, especially at the level of the pancreas, by about 30%. Furthermore, dosimetry studies confirmed the kidney as the dose-limiting organ, and toxicity studies revealed that a nontoxic dose of up to 1,665 kBq could be injected into mice. Efficacy studies indicated a median survival time of 9 wk in the control group, which received only a buffer solution, compared with 19 wk in the group that received 4 injections of 370 kBq at 3-wk intervals. Conclusion: Taken together, these combined data demonstrate the safety, tolerability, and efficacy of [212Pb]Pb-DOTAM-GRPR1, thus warranting further exploration in clinical trials.




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Best Patient Care Practices for Administering PSMA-Targeted Radiopharmaceutical Therapy

Optimal patient management protocols for metastatic castration-resistant prostate cancer (mCRPC) are poorly defined and even further complexified with new therapy approvals, such as radiopharmaceuticals. The prostate-specific membrane antigen (PSMA)–targeted agent 177Lu vipivotide tetraxetan ([177Lu]Lu-PSMA-617), approved after the phase III VISION study, presents physicians with additional aspects of patient management, including specific adverse event (AE) monitoring and management, as well as radiation safety. Drawing on our experience as VISION study investigators, here we provide guidance on best practices for delivering PSMA-targeted radiopharmaceutical therapy (RPT) to patients with mCRPC. After a comprehensive review of published evidence and guidelines on RPT management in prostate cancer, we identified educational gaps in managing the radiation safety and AEs associated with [177Lu]Lu-PSMA-617. Our results showed that providing sufficient education on AEs (e.g., fatigue and dry mouth) and radiation safety principles is key to effective delivery and management of patient expectations. Patient counseling by health care professionals, across disciplines, is a cornerstone of optimal patient management during PSMA-targeted RPT. Multidisciplinary collaboration is crucial, and physicians must adhere to radiation safety protocols and counsel patients on radiation safety considerations. Treatment with [177Lu]Lu-PSMA-617 is generally well tolerated; however, additional interventions may be required, such as dosing modification, medications, or transfusions. Urinary incontinence can be challenging in the context of radiation safety. Multidisciplinary collaboration between medical oncologists and nuclear medicine teams ensures that patients are monitored and managed safely and efficiently. In clinical practice, the benefit-to-risk ratio should always be evaluated on a case-by-case basis.




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Intestinal Lymphatic Biology, Drug Delivery, and Therapeutics: Current Status and Future Directions [Review Article]

Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins, and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20th century focused primarily on the drugs’ physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic, and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs, and lipid-conjugated materials that "hitchhike" onto lymphatic transport pathways. With the increasing development of novel therapeutics such as biologics, there has been interest in whether these therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarize the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies in the future.

Significance Statement

This comprehensive review details the understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients.




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Diffusion Analysis of Intracranial Epidermoid, Head and Neck Epidermal Inclusion Cyst, and Temporal Bone Cholesteatoma [CLINICAL PRACTICE]

BACKGROUND AND PURPOSE:

Intracranial epidermoids temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are typically slow-growing, benign conditions arising from ectodermal tissue. They exhibit increased signal on DWI. While much of the imaging literature describes these lesions as showing diffusion restriction, we investigated these qualitative signal intensities and interpretations of restricted diffusion with respect to normal brain structures. This study aimed to quantitatively evaluate the ADC values and histogram features of these lesions.

MATERIALS AND METHODS:

This retrospective study included children with histologically confirmed diagnoses of intracranial epidermoids, temporal bone cholesteatomas, or head and neck epidermal inclusion cysts. Lesions were segmented, and voxelwise calculation of ADC values was performed along with histogram analysis. ADC calculations were validated with a second analysis software to ensure accuracy. Normal brain ROIs—including the cerebellum, white matter, and thalamus—served as normal comparators. Correlational analysis and Bland-Altman plots assessed agreement among software tools for ADC calculations. Differences in the distribution of values between the lesions and normal brain tissues were assessed using the Wilcoxon rank sum and Kruskal-Wallis tests.

RESULTS:

Forty-eight pathology-proved cases were included in this study. Among them, 13 (27.1%) patients had intracranial epidermoids 14 (29.2%) had head and neck epidermal inclusion cysts, and 21 (43.7%) had temporal bone cholesteatomas. The mean age was 8.67 (SD, 5.30) years, and 27 (56.3%) were female. The intraclass correlation for absolute agreement for lesional ADC between the 2 software tools was 0.997 (95% CI, 0.995–0.998). The intracranial epidermoid head and neck epidermal inclusion cyst, and temporal bone cholesteatoma median ADC values were not significantly different (973.7 versus 875.7 versus 933.2 x 10–6 mm2/s, P = .265). However, the ADCs of the 3 types of lesions were higher than those of 3 normal brain tissue types (933 versus 766, x 10–6 mm2/s, P < .001).

CONCLUSIONS:

The ADC values of intracranial epidermoids, temporal bone cholesteatomas, and head and neck epidermal inclusion cysts are higher than those of normal brain regions. It is not accurate to simply classify these lesions as exhibiting restricted diffusion or reduced diffusivity without considering the tissue used for comparison. The observed hyperintensity on DWI compared with the brain is likely attributable to a relatively higher contribution of the T2 shinethrough effect.




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De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy [RESEARCH ARTICLE]

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).




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Information needs for GPs on type 2 diabetes in Western countries: a systematic review

BackgroundMost people with type 2 diabetes receive treatment in primary care by GPs who are not specialised in diabetes. Thus, it is important to uncover the most essential information needs regarding type 2 diabetes in general practice.AimTo identify information needs related to type 2 diabetes for GPs.Design and settingSystematic review focused on literature relating to Western countries.MethodMEDLINE, Embase, PsycInfo and CINAHL were searched from inception to January 2024. Two researchers conducted the selection process, and citation searches were performed to identify any relevant articles missed by the database search. Quality appraisal was conducted with the Mixed Methods Appraisal Tool. Meaning units were coded individually, grouped into categories, and then studies were summarised within the context of these categories using narrative synthesis. An evidence map was created to highlight research gaps.ResultsThirty-nine included studies revealed eight main categories and 36 subcategories of information needs. Categories were organised into a comprehensive hierarchical model of information needs, suggesting ‘Knowledge of guidelines’ and ‘Reasons for referral’ as general information needs alongside more specific needs on ‘Medication’, ‘Management’, ‘Complications’, ‘Diagnosis’, ‘Risk factors’, and ‘Screening for diabetes’. The evidence map provides readers with the opportunity to explore the characteristics of the included studies in detail.ConclusionThis systematic review provides GPs, policymakers, and researchers with a hierarchical model of information and educational needs for GPs, and an evidence map showing gaps in the current literature. Information needs about clinical guidelines and reasons for referral to specialised care overlapped with needs for more specific information.




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The Ealing domestic abuse initiative: a success story




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Unpicking influence and conflicts of interest in prescribing




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Using the Electronic Health Record to Facilitate Patient-Physician Relationship While Establishing Care [Innovations in Primary Care]




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Chest Pain in Primary Care: A Systematic Review of Risk Stratification Tools to Rule Out Acute Coronary Syndrome [Systematic Review]

PURPOSE

Chest pain frequently poses a diagnostic challenge for general practitioners (GPs). Utilizing risk stratification tools might help GPs to rule out acute coronary syndrome (ACS) and make appropriate referral decisions. We conducted a systematic review of studies evaluating risk stratification tools for chest pain in primary care settings, both with and without troponin assays. Our aims were to assess the performance of tools for ruling out ACS and to provide a comprehensive review of the current evidence.

METHODS

We searched PubMed and Embase for articles up to October 9, 2023 concerning adult patients with acute chest pain in primary care settings, for whom risk stratification tools (clinical decision rules [CDRs] and/or single biomarker tests) were used. To identify eligible studies, a combination of active learning and backward snowballing was applied. Screening, data extraction, and quality assessment (following the Quality Assessment of Diagnostic Accuracy Studies-2 tool) were performed independently by 2 researchers.

RESULTS

Of the 1,204 studies screened, 14 were included in the final review. Nine studies validated 7 different CDRs without troponin. Sensitivities ranged from 75.0% to 97.0%, and negative predictive values (NPV) ranged from 82.4% to 99.7%. None of the CDRs outperformed the unaided judgment of GP’s. Five studies reported on strategies using troponin measurements. Studies using high-sensitivity troponin showed highest diagnostic accuracy with sensitivity 83.3% to 100% and NPV 98.8% to 100%.

CONCLUSION

Clinical decision rules without troponin and the use of conventional troponin showed insufficient sensitivity to rule out ACS in primary care and are not recommended as standalone tools. High-sensitivity troponin strategies are promising, but studies are limited. Further prospective validation in primary care is needed before implementation.




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[PERSPECTIVES] Addressing Biological Questions with Preclinical Cancer Imaging

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.




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[PERSPECTIVES] Restoration of Rod-Derived Metabolic and Redox Signaling to Prevent Blindness

Vision is initiated by capturing photons in highly specialized sensory cilia known as the photoreceptor outer segment. Because of its lipid and protein composition, the outer segments are prone to photo-oxidation, requiring photoreceptors to have robust antioxidant defenses and high metabolic synthesis rates to regenerate the outer segments every 10 days. Both processes required high levels of glucose uptake and utilization. Retinitis pigmentosa is a prevalent form of inherited retinal degeneration characterized by initial loss of low-light vision caused by the death of rod photoreceptors. In this disease, rods die as a direct effect of an inherited mutation. Following the loss of rods, cones eventually degenerate, resulting in complete blindness. The progression of vision loss in retinitis pigmentosa suggested that rod photoreceptors were necessary to maintain healthy cones. We identified a protein secreted by rods that functions to promote cone survival, and we named it rod-derived cone viability factor (RdCVF). RdCVF is encoded by an alternative splice product of the nucleoredoxin-like 1 (NXNL1) gene, and RdCVF was found to accelerate the uptake of glucose by cones. Without RdCVF, cones eventually die because of compromised glucose uptake and utilization. The NXNL1 gene also encodes for the thioredoxin RdCVFL, which reduces cysteines in photoreceptor proteins that are oxidized, providing a defense against radical oxygen species. We will review here the main steps of discovering this novel intercellular signaling currently under translation as a broad-spectrum treatment for retinitis pigmentosa.




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The CheckMate 816 trial: a milestone in neoadjuvant chemoimmunotherapy of nonsmall cell lung cancer

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.